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蛋白质和肽类药物递送系统的最新进展。

Recent advances in protein and peptide drug delivery systems.

作者信息

Malik Dhirendra Kumar, Baboota Sanjula, Ahuja Alka, Hasan Sohail, Ali Javed

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India.

出版信息

Curr Drug Deliv. 2007 Apr;4(2):141-51. doi: 10.2174/156720107780362339.

Abstract

Delivery of therapeutic proteins/peptides has received a considerable amount of attention over the last 10 years, but there are number of limitations to oral delivery of proteins. The barriers to peptide bioavailability after oral administration are intestinal membrane permeability, size, intestinal and hepatic metabolism and lastly solubility. A number of approaches have been used to overcome these limitations. Poor membrane permeabilities of hydrophilic peptides might be overcome by structurally modifying the compound, thus increasing their membrane partition characteristics and their affinity for carrier proteins. Another approach is site specific delivery of the peptides to the most permeable part of the intestine. Metabolism (hepatic and intestinal) of peptides might be controlled by co-administration of competitive enzyme inhibitors, structural modifications and administration of the compound as well as absorbed prodrug that is converted into therapeutically active agent after its absorption. Various delivery systems like prolease technology, nano-particulate and microparticulate delivery system, mucoadhesive delivery of peptides and microspheres have been developed for the delivery of proteins and peptides. Non-conventional delivery systems for proteins are biodegradable and non-biodegradable systems. Besides these, some other approaches for protein and peptide delivery are vector mediated delivery of proteins using adenovirus, macroflux transdermal patches, pulmonary delivery of proteins, delivery of proteins and peptides across blood brain barrier.

摘要

在过去十年中,治疗性蛋白质/肽的递送受到了相当多的关注,但蛋白质口服递送存在一些局限性。口服给药后肽生物利用度的障碍包括肠膜通透性、大小、肠道和肝脏代谢,以及溶解性。已经采用了多种方法来克服这些局限性。亲水性肽较差的膜通透性可以通过对化合物进行结构修饰来克服,从而增加其膜分配特性及其对载体蛋白的亲和力。另一种方法是将肽位点特异性递送至肠道最具通透性的部位。肽的代谢(肝脏和肠道)可以通过联合施用竞争性酶抑制剂、结构修饰、化合物给药以及吸收后转化为治疗活性剂的吸收前体药物来控制。已经开发了各种递送系统,如蛋白酶技术、纳米颗粒和微粒递送系统、肽的粘膜粘附递送和微球,用于蛋白质和肽的递送。蛋白质的非常规递送系统包括可生物降解和不可生物降解的系统。除此之外,蛋白质和肽递送的其他一些方法包括使用腺病毒的蛋白质载体介导递送、宏流透皮贴剂、蛋白质的肺部递送、蛋白质和肽穿过血脑屏障的递送。

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